Combination of the FGFR4 inhibitor PD173074 and 5-fluorouracil reduces proliferation and promotes apoptosis in gastric cancer Expression of Concern in /10.3892/or.2025.9004

Ye,Yan-Wei; Hu,Shuang; Shi,Ying-Qiang; Zhang,Xie-Fu; Zhou,Ye; Zhao,Chun-Lin; Wang,Guo-Jun; Wen,Jian-Guo; Zong,Hong

doi:10.3892/or.2013.2796

December 2013 Volume 30 Issue 6

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December 2013 Volume 30 Issue 6

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Article

Combination of the FGFR4 inhibitor PD173074 and 5-fluorouracil reduces proliferation and promotes apoptosis in gastric cancer

Expression of Concern in: /10.3892/or.2025.9004

Authors:
- Yan-Wei Ye
- Shuang Hu
- Ying-Qiang Shi
- Xie-Fu Zhang
- Ye Zhou
- Chun-Lin Zhao
- Guo-Jun Wang
- Jian-Guo Wen
- Hong Zong
View Affiliations / Copyright

Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China, Department of Stomach and Soft Tissue Sarcoma Surgery, Shanghai Cancer Center, Fu Dan University, Shanghai, P.R. China, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
Pages: 2777-2784
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Published online on: October 11, 2013

https://doi.org/10.3892/or.2013.2796
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Abstract

Our previous findings revealed that FGFR4 may be a novel therapeutic target for gastric cancer. The aim of the present study was to explore the effects of a combination of PD173074 (PD) and 5-fluorouracil (5-Fu) on the biological behavior of gastric cancer cell lines and the relevant mechanisms involved. MKN45, a gastric cancer cell line, was treated with each single agent alone or a combination of FGF19, PD and 5-Fu. Then, a series of functional assays were performed using CCK-8 assay and flow cytometry. Western blot analysis was used to determine the expression of signaling pathway and downstream-related molecules in the MKN45 cells following the different treatments. As the concentration of PD and 5-Fu increased, the cell viability gradually decreased; the viability of the combination group was less than the viability following single administration. Western blot analysis showed that FGFR4 expression was weak in the 5-Fu-treated groups when compared with the control. PD markedly increased the apoptosis rate of MKN45 cells when compared to the control; the apoptosis rate in the cells treated with the combination of PD and 5-Fu was higher than that in the cells following single treatment. Furthermore, PD reduced the expression of p-ERK and Bcl-xl and increased caspase-3 expression. Inhibition of the activity of FGFR4 may be the main mechanisms of PD effect while 5-Fu reduced FGFR4 expression. Furthermore, the effects of the combination of 5-Fu and PD in inhibiting proliferation, increasing apoptosis and arresting cell cycle were superior to these effects following the single agent treatments, suggesting that the two drugs applied in combination may contribute to the effective treatment of gastric cancer.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Combination of the FGFR4 inhibitor PD173074 and 5-fluorouracil reduces proliferation and promotes apoptosis in gastric cancer

Expression of Concern in: /10.3892/or.2025.9004

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Abstract

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